Safety of switching from vitamin K antagonists to dabigatran or rivaroxaban in daily care – results from the Dresden NOAC registry

Abstract

AIMVitamin-K antagonists (VKA) and non-vitamin-K dependent oral anticoagulants (NOAC) have been approved for anticoagulation in venous thromboembolism (VTE) and atrial fibrillation and patients previously treated with VKA are switched to NOAC therapy. Safety data for this switching are urgently needed. METHODSUsing data from a large regional prospective registry of daily care NOAC patients, we evaluated the safety of switching anticoagulation from VKA to dabigatran or rivaroxaban. Switching procedures and cardiovascular and bleeding events occurring within 30 days after switching were centrally adjudicated. RESULTSBetween 1 October 2011 and 18 June 2013, 2231 patients were enrolled. Of these, 716 patients were switched from VKA to NOAC. Only 410 of the 546 evaluable patients (75.1%) had a recorded INR measurement within the 10 days preceding or following the end of VKA treatment (mean INR 2.4). As of day 30, major bleeding complications were rare (0.3%; 95% CI 0.0, 1.0) with an overall bleeding rate of 12.2% (95% CI 9.8, 14.8). Major cardiovascular events occurred in 0.8% (95% CI 0.3, 1.8). There was no significant difference in outcome event rates between the subgroups of patients with or without INR testing. CONCLUSIONIn daily care, only 75% of VKA patients have an INR measurement documented before NOAC are started. On average, NOAC are started within 2 to 5 days after the last intake of VKA. However, at 30 days follow-up cardiovascular events or major bleedings were rare both in patients with and without INR testing. However, switching procedures need to be further evaluated in larger cohorts of patients. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Patients on vitamin-K antagonists (VKA) need to have their INR tested before a transition to a different anticoagulant. Different INR thresholds exist for different anticoagulants and for different indications, but existing recommendations have never been analyzed. • Consequently, the recommendations for switching from VKA to non-vitamin-K dependent direct oral anticoagulants (NOAC or DOAC) in the summary of product characteristics (SMPCs) of the NOACs are not evidence based.• In daily practice, considerable concerns are raised about these recommendations (initiation of NOAC at INR values <2.0 for apixaban and dabigatran in SPAF, INR <2.5 for rivaroxaban in venous thromboembolism (VTE) and INR <3.0 for rivaroxaban in stroke prevention in non-valvular atrial fibrillation (SPAF).• In the Rocket-AF trial, major bleeding complications were highest in the subgroup of rivaroxaban patients with VKA pre-treatment compared with the subgroups of patients without VKA pre-treatment or the subgroup of pre-treated patients randomized to warfarin. This could be an indicator that the transition from VKA pre-treatment to NOAC increases bleeding risks. WHAT THIS STUDY ADDS• In daily practice, only 75% of all patients had a recorded INR measurement within 10 days before or after the end of VKA treatment. The baseline characteristics of patients receiving INR testing were not different ...

Management of Patients on Non–Vitamin K Antagonist Oral Anticoagulants in the Acute Care and Periprocedural Setting: A Scientific Statement From the American Heart Association

“…111,112 In a matched-cohort study of AF patients, there was no association of transitioning from a VKA to either dabigatran or rivaroxaban compared with remaining on VKA therapy for embolic or bleeding events at a median follow-up of 10 months. 112 Data from a large regional prospective registry showed clinical events were relatively infrequent in the 30-day period after VKA to NOAC transitions despite only 75% of patients having an INR measurement before NOAC initiation.…”

Doustne antykoagulanty nowej generacji — aspekty praktyczne. Stanowisko Sekcji Farmakoterapii Sercowo-Naczyniowej Polskiego Towarzystwa Kardiologicznego

“…Dowodzą tego między innymi dane z Dresden NOAC Registry [20]. Jednym z celów tego rejestru była ocena bezpieczeństwa konwersji z antykoagulantów VKA do NOAC.…”

Direkte orale Antikoagulantien und Medikamenteninteraktionen

“…Allerdings wurde auf Grund von Studiendaten das Blutungsrisiko bei der kombinierten Gabe im Vergleich zur alleinigen Gabe von Rivaroxaban nicht als klinisch relevant bewertet [8]. Erythromycin ist ein moderater Inhibitor von CYP3A4 und P-gp und führt bei gleichzeitiger Applikation ebenfalls zu einer leicht erhöhten Rivaroxaban-Exposition, die jedoch nicht als klinisch relevant bewertet wird [8] [25]. Das Blutungsrisiko kann einerseits erhöht werden, wenn sich durch Medikamenteninteraktionen der Plasmaspiegel des DOACs erhöht, andererseits aber auch wenn die bestehende Medikation bereits eine Störung im Gerinnungssystem bewirkt.…”